1. Field of the Invention
This invention relates to a process for manufacturing an optically active (S)-3,4-epoxybutyric acid salt and more particularly, to a method for manufacturing (S)-3,4-epoxybutyric acid salt expressed by the following formula 1, wherein an optically active (S)-3-hydroxybutyrolactone is employed to undergo an economical ring-opening reaction and epoxydation so that its chiral center is maintained in an original form. ##STR2##
Wherein, R.sub.1 represents alkali metal atom, alkaline earth metal atom, alkylamin group or quarternary amine group. PA1 Where, R.sub.1 is determined depending on the kinds of base used and represents alkali metal atom, alkaline earth metal atom, alkylamine group or quarternary amine group; R.sub.2 represents halogen group which may enable the epoxidation; R.sub.3 represents hydrogen atom or acyl group. PA1 Where, R.sub.1, R.sub.2 and R.sub.3 are the same as defined above, respectively.
2. Description of the Related Art
An (S)-3,4-epoxybutyric acid salt expressed by the above formula 1 is a pivotal compound as an indispensable intermediate of various chiral drugs because of the synethetic usefulness of epoxy group. In particular, since (S)-3,4-epoxybutyric acid salt expressed by the above formula 1 has a better reactivity under aqueous solution, its availability in various chemical reaction has a broader scope in related fields.
The optically active (S)-3,4-epoxybutyric acid salt has the industrial application as raw material of drugs which may be contained in the cerebral enhancers and senile dementia drugs, antibiotics, antihypertensives and antihyperlipidemia.
The typical manufacturing methods related to (S)-3,4-epoxybutyric acid salt developed hitherto and some compounds with similar reactivity are as follows:
A method of manufacturing (S)-3,4-epoxybutyric acid salt was to introduce epoxy group sterically via asymmetric epoxydation and oxidation in a sequence but the extremely low yield and optical purity of the desired compound (yield: 11.about.25%, optical purity: 55%) proven to be inadequate for industrial use [J. Org. Chem., 49,3707(1984)].
According to another method [(Helv. Chim. Acta, 70, 142(1987) and European Pat. No. 237,983], it disclosed a method of manufacturing (S)-3,4-epoxybutyric acid salt, wherein a racemic 3,4-epoxybutyric acid ester was prepared and followed by the use of an enzyme based on an optical separation method. This method was proven to have been effective in optical purity but more than 50% yield could not be obtained in consideration of prolonged reaction time, maintenance of reaction conditions in enzyme and optical separation reaction in the light of biological reaction.
In addition, a method of manufacturing (S)-3,4-epoxybutyric acid ester from (S)-3-hydroxybutyrolactone was disclosed (Tetrahedron Letters 28, 1781(1987); Tetrahedron 46, 4277 (1990) and International Patent Publication No. WO93/06826). Its manufacturing process is described in the following scheme 1. ##STR3##
The scheme 1 has recognized some disadvantages in that a) with a high-priced iodotrimethyl silane (SiI(CH.sub.3).sub.3) reagent for iodination and esterification, the reaction should be performed in the presence of anhydrous solvent, b) during epoxydation, a high-priced silver oxide (AgO) reagent should be uneconomically employed, and c) since (S)-3,4-epoxybutyric acid ester, so prepared from the conventional methods has no reactivity in an aqueous solution, its scope of use is extremely restricted. For example, a glycine derivative is insoluble to organic solvents, so it should be modified with benzylaldehye first so as to enhance its solubility to organic solvent during the amination between (S)-3,4-epoxybutyric acid ester and glycine derivative. 4-Hydroxy -2-butenic acid ester is also generated as a byproduct due to elimination reaction associated with the basicity of glycine derivative, when it reacts with (S)-3,4-epoxybutyric acid ester.
By contrast, (S)-3,4-epoxybutyric acid salt, a final product of this invention having a better reactivity in an aqueous solution may be directly aminated with glycine or glycine derivative in an aqueous solution, thus simplifying the complicated manufacturing process.